Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility.

The genus Wolbachia is an archetype of maternally inherited intracellular bacteria that infect the germline of numerous invertebrate species worldwide. They can selfishly alter arthropod sex ratios and reproductive strategies to increase the proportion of the infected matriline in the population. The most common reproductive manipulation is cytoplasmic incompatibility, which results in embryonic lethality in crosses between infected males and uninfected females. Females infected with the same Wolbachia strain rescue this lethality. Despite more than 40 years of research and relevance to symbiont-induced speciation, as well as control of arbovirus vectors and agricultural pests, the bacterial genes underlying cytoplasmic incompatibility remain unknown. Here we use comparative and transgenic approaches to demonstrate that two differentially transcribed, co-diverging genes in the eukaryotic association module of prophage WO from Wolbachia strain wMel recapitulate and enhance cytoplasmic incompatibility. Dual expression in transgenic, uninfected males of Drosophila melanogaster crossed to uninfected females causes embryonic lethality. Each gene additively augments embryonic lethality in crosses between infected males and uninfected females. Lethality associates with embryonic defects that parallel those of wild-type cytoplasmic incompatibility and is notably rescued by wMel-infected embryos in all cases. The discovery of cytoplasmic incompatibility factor genes cifA and cifB pioneers genetic studies of prophage WO-induced reproductive manipulations and informs the continuing use of Wolbachia to control dengue and Zika virus transmission to humans.

The phage gene wmk is a candidate for male killing by a bacterial endosymbiont.

Wolbachia are the most widespread maternally-transmitted bacteria in the animal kingdom. Their global spread in arthropods and varied impacts on animal physiology, evolution, and vector control are in part due to parasitic drive systems that enhance the fitness of infected females, the transmitting sex of Wolbachia. Male killing is one common drive mechanism wherein the sons of infected females are selectively killed. Despite decades of research, the gene(s) underlying Wolbachia-induced male killing remain unknown. Here using comparative genomic, transgenic, and cytological approaches in fruit flies, we identify a candidate gene in the eukaryotic association module of Wolbachia prophage WO, termed WO-mediated killing (wmk), which transgenically causes male-specific lethality during early embryogenesis and cytological defects typical of the pathology of male killing. The discovery of wmk establishes new hypotheses for the potential role of phage genes in sex-specific lethality, including the control of arthropod pests and vectors.

Treatment of distal radius fractures with locking plates: an update.

Internal fixation with volar locking plates has revolutionized the treatment of distal radius fractures. Manufacturers have introduced plate designs that closely follow the anatomy of the distal radius. However, use of volar plates has also led to the emergence of new types of complications. While the use of monoaxial or polyaxial locking screws and of minimally invasive techniques (arthroscopy, preservation of pronator quadratus) increases the cost of the surgical procedure, it results in a tangible benefit for patients, allowing them to move their wrist almost immediately after surgery and to quickly regain their autonomy. We reviewed the literature to analyze the level of proof.

Plate fixation of distal radius fracture and related complications.

INTRODUCTION: Distal radius fractures are common. In cases where surgical treatment is needed, volar plates can be used to obtain stable, long-lasting fixation. The design of these plates has continually improved over the years, but complications remain a problem. PURPOSE: The goal of this study was to evaluate the types of complications that occur with different types of volar plates with a view towards preventing them. MATERIALS AND METHODS: The emergency department at our hospital saw 524 patients with distal radius fractures between 2006 and 2008. Some of these were treated surgically with a volar plate. All of the post-operative complications were documented. RESULTS: With a minimum follow-up of 6 months, 152 patients who had undergone plate fixation were reviewed: 31 had received plates with non-locking screws or uniaxial locking screws and 121 had received plates with polyaxial locking screws. The complication rate was similar in these two groups (16.1 and 16.5%, respectively). The main complications were tendon ruptures and problems related to the plate itself. DISCUSSION: Plate-related complications have been described in published studies, but few of these studies link them to the plate design or surgical technique. Manufacturers must continue to refine these plates to minimise their thickness while keeping their strength. Surgeons must be sure to use a highly exacting technique.

Displaced humeral shaft fractures: Assessment of fracture union and complications following dual plate fixation using an anterior approach.

The humeral bone is subject to torsional forces. In case of displaced shaft fractures, internal fixation remains the standard of care. This retrospective two-center study assessed the fracture union rate and complications after dual 3.5 mm locking compression plate (LCP) fixation using an anterolateral approach. Over a 9-year period, 38 patients underwent surgery in two centers. They had a mean age of 53.7 years (15-97, ± standard deviation (SD) 26) and there were three open fracture cases (7.9 %). The dominant side was affected in 21 cases (55.3 %) and there were 11 polytrauma patients (29 %). Mean operative time was 78 min (40-124, ± 19.8 SD). Patients were treated with dual 3.5 mm LCP fixation (6 screws on either side of the fracture line, anterolateral approach without a tourniquet). The first two orthogonal views showing at least 3 cortical bridges out of 4 determined fracture healing, as assessed by two independent raters. Pre- and postoperative complications were tabulated. Clinical outcomes included range of motion (ROM) and return to activities, while functional outcomes were assessed with the Disability of the Arm Shoulder and Hand (DASH), the Constant score, the Subjective Shoulder Score (SSV) and the Mayo Elbow Performance Score (MEPS). Minimum follow-up was 1 year. Four patients were given a shoulder immobilizer to wear for 3 weeks; immediate mobilization was the standard of care for the other patients. Fracture union was achieved in all cases within a mean of 11.7 weeks (6-28 ± 7.1 SD) without any heterotopic ossification of the brachialis muscle. There were eight patients with preoperative radial nerve palsy and two cases of postoperative palsy. There was one surgical site infection (2.6 %). Return to work for active patients was possible in 87 % of cases within a mean of 23 weeks (6-72 ± 11 SD). The Constant score was 84.6 (35-100, ± 13.4 SD), the SSV score was 80.7 (60-100, ± 8.2 SD), the DASH score was 13.5 (0-38.3, ± 8.8 SD) and the MEPS score was 85 (55-100, ± 11.9 SD). Traditional fixation methods provide little control over torsional forces, leading to non-union rates between 3 % and 12 % and delayed union (12 to 20 weeks). The simplicity of the technique described here, and the short operative time, may help explain the low infection rate. Dual plate fixation makes it possible to use more screws and allows nerve exploration and decompression in case of preoperative nerve palsy. Dual plate fixation to treat humeral shaft fractures is a simple and reliable technique.

Reproducibility of the Mayo and Schatzker classification systems in proximal ulna fractures.

INTRODUCTION: A fracture classification system should provide a reliable and reproducible means of communication between different parties. It should be logical and understandable, with few categories to memorize. The aim of this study was to determine the intra- and interobserver reliability of the Schatzker and Mayo classification systems for the assessment of proximal ulna fractures. MATERIALS AND METHODS: Intra- and interobserver reliability studies were conducted on 39 X-rays of injured elbows drawn randomly from 74 cases previously used in a series on predictors of ulnohumeral osteoarthritis in proximal ulna fractures. Ten observers independently reviewed these X-rays on 2 separate occasions 3 months apart. The fracture type was assessed according to the Schatzker and Mayo classification systems during each reading session. Cohen's and Fleiss' kappa were used to measure the intra- and interobserver reliability. RESULTS: The Schatzker classification had a fair interobserver reliability for the first (Schatzker R1, Fleiss' κ: 0.394) and second (Schatzker R2, Fleiss' κ: 0.351) readings. The mean intraobserver reliability value between the 10 reviewers for the Schatzker classification was rated as substantial (0.61). The Mayo classification had a fair interobserver reliability for the first (Mayo R1, Fleiss' κ: 0.278) and second (Mayo R2, Fleiss' κ: 0.292) readings. The mean intraobserver reliability value between the 10 reviewers for the Mayo classification was rated as fair (0.52). DISCUSSION: The classification systems for proximal ulna fractures showed poor reproducibility between the different observers since they had low interobserver agreement values. Nevertheless, their use remained reliable since the measured intraobserver agreement value was deemed substantial. LEVEL OF EVIDENCE: IV; retrospective.

Epidemiology of upper limb chronic exertional compartment syndrome (CECS) in the French Motorcycle Federation racers: Results of a national questionnaire-based study.

Upper limb chronic exertional compartment syndrome (CECS) has been described in amateur and professional motorcycle racers, but there is no published data about its prevalence. The purpose of this study was to define the awareness, prevention and prevalence of this syndrome in licensed motorcycle racers in competition in France. Secondary purposes were to determine the functional impact of CECS and post-treatment outcomes. The 20,641 licensed racers in competition of the French Motorcycle Federation were sent a self-assessment questionnaire about upper limb pain and CECS physical examination findings, functional impact and treatment outcomes. The satisfaction level was assessed after each type of treatment. Acceptability rate was 6.35% with 1311 racers responding. CECS was unknown by 29% of racers. Prevention methods were unknown by 10% of racers. Less than 50% of racers modified their bikes. The prevalence of upper limb CECS in competitive racers was 9%: 8.7% forearm, 0.2% thenar, 0.1% hypothenar and 0.4% first dorsal interosseus compartments. The prevalence was 16% in international level racers, 11% in national level racers and 7.3% in regional level racers. A quarter of racers were satisfied or very satisfied with the outcomes of conservative therapy and rehabilitation. Only 67 racers underwent surgical treatment for their upper limb CECS: 31 by open fasciotomy, 23 by minimally invasive fasciotomy and 13 by endoscopy-assisted compartment release. In these 67 racers, the mean visual analog score for pain improved significantly (p < 0.001 95% CI [3.1-4.5]) with 81% satisfied or very satisfied with surgery outcomes. This epidemiologic self-assessment questionnaire for upper limb CECS is a new concept. This study screened for CECS and offer information regarding evaluation, treatment, and management.

Anatomical basis for ultrasound-guided regional anaesthesia at the junction of the axilla and the upper arm.

PURPOSE: Ultrasound (US) has emerged in the field of regional anaesthesia in the past few years, as it allows physicians to simultaneously see the needle, the targeted nerves, and the vessels to avoid. Nevertheless, anatomical knowledge is essential for identifying all of the structures seen on the US screen. US also allows an in vivo approach to the variations of nerves and vessels. The aim of this study was to describe the anatomical structures of the axilla through a dissection, an anatomical section and US images performed during daily regional anaesthesia. This work will also discuss the usefulness of US in studying anatomical variations of vasculonervous structures. METHODS: The axillary region of an embalmed adult cadaver was dissected in the department of Anatomy, and anatomical sections of another embalmed and frozen cadaver were also performed. During the same period, fortuitous anatomical variations discovered during daily routine axillary US-guided nerve blocks were recorded in the department of Anaesthesiology. RESULTS: The anatomical dissection and sections allowed correlations to be made and structures to be identified on the US images. The most frequent anatomical variations found were double axillary artery, numerous axillary veins, variant location of the musculocutaneous nerve and posterior location of the brachial plexus in relation to the axillary artery. CONCLUSION: Anatomical knowledge is of major importance for US-guided regional anaesthesia. US scan offers a new approach to anatomical variations of the vasculonervous bundle at the junction of the axilla and the upper arm.

Scapholunate kinematics after flexible anchor repair.

The scapholunate joint is one of the keystones of the wrist kinematics, and its study is difficult due to the carpal bones size and the richness of surrounding ligaments. We propose a new method of quantitative assessment of scapholunate kinematics through bone motion tracking in order to investigate scapholunate ligament lesion as well as repair techniques. On 6 intact wrists, steel beads were inserted into the bones of interest to track their motions. Experimental set up allowed wrist flexion extension and radio-ulnar deviation motions. Low-dose bi-planar radiographs were performed each 10° of movement for different configurations: 1) intact wrist, 2) scapholunate ligament division, 3) repair by soft anchors at the posterior then 4) anterior part. Beads' 3D coordinates were computed at each position from biplanar X-Rays, allowing accurate registration of each wrist bone. The Monte Carlo sensitivity study showed accuracy between 0.2° and 1.6 ° for the scaphoid and the lunate in motions studied. The maximum flexion-extension range of motion of the scaphoid significantly decreased after anterior repair from 73° in injured wrist to 62.7°. The proposed protocol appears robust, and the tracking allowed to quantify the anchor's influence on the wrist kinematics.

[Articular reconstructions by a costochondral grafting (or osteochondral costal grafting)]. / Utilisation du greffon cartilagineux (ou ostéocartilagineux) costal en reconstruction articulaire.

We describe a novel technique of costochondral autografting for the treatment of trapeziometacarpal arthritis, radioscaphoid osteoarthritis, malunion of the distal end of the radius, and osteoarticular loss of the MP joints of long fingers. The costal graft harvest technique is always the same. A 5-cm horizontal incision is made over the 9th rib, and the rib is exposed at the osteocartilaginous junction. Cartilaginous grafts are harvested with a scalpel, and osteocartilaginous grafts with a saw. Since 1992, 116 patients with trapezio-metacarpal arthritis have been treated by partial trapeziectomy and autologous rib cartilage grafting. One hundred patients were reviewed with an average follow-up of 5.6 years. The results were better than those of trapeziectomy with tendon interposition or ligamentous reconstruction, owing to good stability of the thumb ray height. For the treatment of radioscaphoid osteoarthritis following scaphoid non union or chronic scapholunate instability, partial carpal arthrodesis and resection of the first row are the classical techniques. As an alternative to these procedures, 18 patients were treated by resection of the proximal portion of the scaphoid and insertion of an osteochondral costal autograft. Mean follow-up is 4.1 years. The results are excellent or good in 15 cases, fair in 2 cases, and poor in 1 case (luxation of the graft). Four patients with articular malunion of the distal radius received an osteocartilaginous costal graft to reconstruct the articular surface of the radius while avoiding partial or total arthrodesis of the wrist. Four patients with segmental osteoarticular loss of the longfingers were treated with the same technique, thereby avoiding silicone arthroplasty. We review the literature on cartilaginous rib grafts in maxillofajcial and orthopaedic surgery. In our experience, MRI and biopsy show viable cartilage but also histologic changes such as revascularization, fibrous transformation and bone metaplasia.

Distal radius anatomy applied to the treatment of wrist fractures by plate: a review of recent literature.

Few studies on the anatomy of the radial epiphysis have been published in the past 10 years. However, with the availability of new intra- and extra-medullary implants and the recent rash of avoidable iatrogenic injuries, now is the time for a more detailed description of the metaphyseal-epiphyseal regions in the distal radius. Published studies on distal radius anatomy in recent years have focused on three aspects: distal limit and watershed line, dorsal tubercle, and wrist columns. Furthermore, a fresh look at distal radius biomechanics shows that the loads experienced by the distal radius vary greatly. This information should be taken into account during volar plating of distal radius fractures.

Rib cartilage grafting in upper limb surgery: an overview.

INTRODUCTION: Used routinely in maxillofacial reconstructive surgery, the chondrocostal graft is also used in hand surgery. The purpose of this overview was to analyze at long follow-up the radiological and histological evolution of this autograft, in the hand and wrist surgery. MATERIALS AND METHODS: Since 1992, 144 patients have benefitted from a chondrocostal autograft: 116 osteoarthritis of the thumb carpometacarpal joint, 18 radioscaphoid arthritis, six articular malunions of the distal radius, four kienbock, and four traumatic loss of cartilage of the PIP joint. Magnetic Resonance Imaging (MRI) was performed in 19 patients and histological study in 12 patients with a mean follow-up of 68 months (4-159). RESULTS: Whatever the indication, the reconstruction by a chondrocostal or ostochondrocostal graft has allowed us to obtain satisfactory clinical results at long follow-up. The main question was the viability of the graft. The radiological study has shown the non-wear of the graft and a certain degree of ossification. The MRI confirmed a very small degree of osseous metaplasia but its viability. The biopsies showed a neo-vascularization of the cartilage. CONCLUSION: Despite the strong mechanical strain in the hand and wrist, the chondrocostal graft is a biological arthroplasty, trustworthy and secure at long time even if it can cause infrequent complications inherent to this type of surgery. Despite the inevitable histological modification, the cartilage remains alive and is of satisfactory quality at long term follow-up and fulfilling the requirements for interposition and reconstruction of an articular surface.

The relative importance of DNA methylation and Dnmt2-mediated epigenetic regulation on Wolbachia densities and cytoplasmic incompatibility.

Wolbachia pipientis is a worldwide bacterial parasite of arthropods that infects germline cells and manipulates host reproduction to increase the ratio of infected females, the transmitting sex of the bacteria. The most common reproductive manipulation, cytoplasmic incompatibility (CI), is expressed as embryonic death in crosses between infected males and uninfected females. Specifically, Wolbachia modify developing sperm in the testes by unknown means to cause a post-fertilization disruption of the sperm chromatin that incapacitates the first mitosis of the embryo. As these Wolbachia-induced changes are stable, reversible, and affect the host cell cycle machinery including DNA replication and chromosome segregation, we hypothesized that the host methylation pathway is targeted for modulation during cytoplasmic incompatibility because it accounts for all of these traits. Here we show that infection of the testes is associated with a 55% increase of host DNA methylation in Drosophila melanogaster, but methylation of the paternal genome does not correlate with penetrance of CI. Overexpression and knock out of the Drosophila DNA methyltransferase Dnmt2 neither induces nor increases CI. Instead, overexpression decreases Wolbachia titers in host testes by approximately 17%, leading to a similar reduction in CI levels. Finally, strength of CI induced by several different strains of Wolbachia does not correlate with levels of DNA methylation in the host testes. We conclude that DNA methylation mediated by Drosophila's only known methyltransferase is not required for the transgenerational sperm modification that causes CI.

Wolbachia: Can we save lives with a great pandemic?

Wolbachia pipientis is the most common bacterial infection in the animal world and wields a vast influence on invertebrate reproduction, sex determination, speciation, and behavior worldwide. These avenues of research have made seminal gains, including the latest use of Wolbachia to alter mosquito populations and a strengthened focus on using anti-Wolbachia therapies against filarial nematode infections. This work is further bolstered by a more refined knowledge of Wolbachia biology spanning mechanisms to relevance. Here we tally the most up-to-date knowledge in the field and review the immense implications that this global infection has for the basic and applied life sciences.

Rib cartilage graft for posttraumatic or degenerative arthritis at wrist level: 10-year results.

Background Posttraumatic arthritides of the radiocarpal joint, secondary to scaphoid nonunion advanced collapse (SNAC), scapholunate advanced collapse (SLAC), or Kienböck disease or in cases of intraarticularmalunion of the distal radius, are classically solved by some type of arthrodesis procedure. Osteochondral grafting provides a possible motion-sparing option that can diminish pain in the active patient. Description of Technique A chondrocostal graft harvested from the ninth rib was inserted and fixed with a plate in place of the articular defect in cases of a malunited intra-articular distal radius fracture (7 cases) or to replace the proximal pole of the scaphoid in cases of SNAC or SLAC (18 cases). In Kienböck disease, the graft was inserted as a free cartilage spacer (4 cases). Results Harvesting the graft from the ninth rib had minimal morbidity without pleural injury in the reported series. Graft union was achieved in all cases of fixation. No graft resorption or necrosis were observed on X-ray and magnetic resonance imaging (MRI) evaluation at the longest follow-up of 10 years. Histological analysis performed at the time of plate removal showed the vitality of the graft. Two thirds of the patients had excellent or good results using the Green and O'Brien score. Conclusions Reconstruction of a partially destroyed articular surface using a costal graft is reliable and provides an alternative option for resurfacing the articular surface with viable cartilage.

Luciferase inhibition by a novel naphthoquinone.

The novel naphthoquinone 12,13-dihydro-N-methyl-6,11,13-trioxo-5H-benzo[4,5]cyclohepta[1,2-b]naphthalen-5,12-imine (hereafter called TU100) was created as a potential chemotherapeutic agent. Previous work showed it is an irreversible inhibitor of type I and II topoisomerases that alkylates specific enzyme thiols. While analyzing the effect of TU100 on cancer cells, we discovered it is a potent inhibitor of luciferase derived from both Photinus pyralis (fireflies) and Renilla reniformis (sea pansy). Pre-incubation experiments showed that TU100 does not irreversibly inactivate luciferase, indicating its mechanism is different from that observed with topoisomerases. Firefly luciferase generates light using ATP and luciferin as substrates (bioluminescence). An examination of TU100 inhibition at varying substrate concentrations revealed the drug is uncompetitive with respect to ATP and competitive with respect to luciferin. The TU100 binding constant (K(I)) is 2.5±0.7 µM as determined by Dixon plot analysis. These data suggest TU100 specifically binds the luciferase-ATP complex and prevents its interaction with luciferin. Given the novel structure of TU100, unique mechanism of action, and ability to target luciferase from different species, these results identify TU100 as an important new reagent for investigating and regulating bioluminescent enzymes.

A user-assisted approach to visualizing multidimensional images.

We present a new technique for fusing together an arbitrary number of aligned images into a single color or intensity image. We approach this fusion problem from the context of Multidimensional Scaling (MDS) and describe an algorithm that preserves the relative distances between pairs of pixel values in the input (vectors of measurements) as perceived differences in a color image. The two main advantages of our approach over existing techniques are that it can incorporate user constraints into the mapping process and allows adaptively compressing or exaggerating features in the input in order to make better use of the output's limited dynamic range. We demonstrate these benefits by showing applications in various scientific domains and comparing our algorithm to previously proposed techniques.